US3247186A - Certain 2-lower alkoxy-5-phenyl-3h-1, 4-benzodiazepine 4-oxide compounds and their preparation - Google Patents
Certain 2-lower alkoxy-5-phenyl-3h-1, 4-benzodiazepine 4-oxide compounds and their preparation Download PDFInfo
- Publication number
- US3247186A US3247186A US318783A US31878363A US3247186A US 3247186 A US3247186 A US 3247186A US 318783 A US318783 A US 318783A US 31878363 A US31878363 A US 31878363A US 3247186 A US3247186 A US 3247186A
- Authority
- US
- United States
- Prior art keywords
- phenyl
- benzodiazepine
- preparation
- formula
- lower alkoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- MTNWQRGOHOXCFV-UHFFFAOYSA-N 7-chloro-2-methoxy-4-oxido-5-phenyl-3h-1,4-benzodiazepin-4-ium Chemical compound [O-][N+]=1CC(OC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 MTNWQRGOHOXCFV-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- QNRATNLHPGXHMA-XZHTYLCXSA-N (r)-(6-ethoxyquinolin-4-yl)-[(2s,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]methanol;hydrochloride Chemical compound Cl.C([C@H]([C@H](C1)CC)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OCC)C=C21 QNRATNLHPGXHMA-XZHTYLCXSA-N 0.000 description 1
- SLPUGTRSHPWDLZ-UHFFFAOYSA-N 5-phenyl-1,4-benzodiazepin-2-one Chemical compound C=12C=CC=CC2=NC(=O)C=NC=1C1=CC=CC=C1 SLPUGTRSHPWDLZ-UHFFFAOYSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- -1 for example Chemical group 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
Definitions
- R is halogen or trifluoromethyl. Also preferred are compounds of Formula I wherein R is hydrogen or is a halogen substituent in the ortho-position.
- halogen includes all four halogens, i.e. fluorine, iodine, bromine and chlorine. Preferred are chlorine, fluorine and bromine.
- lower alkyl includes saturated straight and branched chain hydrocarbon moieties, for example, methyl, ethyl, propyl, isopropyl and the like.
- the compounds of Formula I above can be prepared by treating a compound of the formula NH-C wherein R and R have the same meaning as above with a diazoalkane of the formula R (III) wherein R is lower alkylene, i.e. a moiety of the formula 3,247,186 Patented Apr. 19, 1966 solvent, for example, a lower alkanohor ethers such as lower alkyl ethers, diglyme and the like.
- the compounds of Formula I are useful as muscle relaxants and central nervous system depressants. They can be administered internally, for example, orally or parenterally, in conventional pharmaceutical dosage forms, such as solid forms, for example, tablets, dragees, capsules or the like and liquid forms, such as suspensions, emulsions, solutions or the like. They can be combined with pharmaceutical excipients or carriers and can be submitted to conventional pharmaceutical expedients, for example, sterilization.
- the compounds of Formula I above are also useful as chemical intermediates.
- they via reaction with methylamine, they can be converted into Z-methylamino-S-phenyl-1,4-3H-benzodi'azepine-4-oxides which are known compounds of pharmaceutical utility. This conversion is not a part of this invention but is mentioned her n only in the interest of comprehensiveness.
- a method for the preparation of a compound of claim 1 which comprise-s treating a compound of the formula 3 4 wherein R and R have the same meaning as in claim 1, 6.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US318783A US3247186A (en) | 1963-10-25 | 1963-10-25 | Certain 2-lower alkoxy-5-phenyl-3h-1, 4-benzodiazepine 4-oxide compounds and their preparation |
| CH1301964A CH440300A (de) | 1963-10-25 | 1964-10-07 | Verfahren zur Herstellung von Benzodiazepin-Derivaten |
| DE19641445911 DE1445911A1 (de) | 1963-10-25 | 1964-10-09 | Verfahren zur Herstellung von Benzodiazepin-Derivaten |
| IL22232A IL22232A (en) | 1963-10-25 | 1964-10-11 | History of benzodiazepines and the process for their production |
| FR991810A FR3878M (fr) | 1963-10-25 | 1964-10-17 | Médicament a base de dérivés de benzodiazépine. |
| DK516264AA DK105983C (da) | 1963-10-25 | 1964-10-19 | Fremgangsmåde til fremstilling af 2-alkoxy-5-aryl-3H-1,4-benzodiazepin-4-oxider. |
| FR991849A FR1442304A (fr) | 1963-10-25 | 1964-10-19 | Procédé pour la préparation de dérivés de benzodiazépine |
| BR163545/64A BR6463545D0 (pt) | 1963-10-25 | 1964-10-20 | Processo para a preparacao de derivados de benzodiazepina |
| GB43159/64A GB1058738A (en) | 1963-10-25 | 1964-10-22 | Benzdiaz[1,4]epines and a process for the manufacture thereof |
| NL6412300A NL6412300A (da) | 1963-10-25 | 1964-10-22 | |
| BE654734D BE654734A (da) | 1963-10-25 | 1964-10-23 | |
| ES0305264A ES305264A1 (es) | 1963-10-25 | 1964-10-24 | Un procedimiento para la preparacion de derivados de benzodiazepina. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US318783A US3247186A (en) | 1963-10-25 | 1963-10-25 | Certain 2-lower alkoxy-5-phenyl-3h-1, 4-benzodiazepine 4-oxide compounds and their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3247186A true US3247186A (en) | 1966-04-19 |
Family
ID=23239560
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US318783A Expired - Lifetime US3247186A (en) | 1963-10-25 | 1963-10-25 | Certain 2-lower alkoxy-5-phenyl-3h-1, 4-benzodiazepine 4-oxide compounds and their preparation |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US3247186A (da) |
| BE (1) | BE654734A (da) |
| BR (1) | BR6463545D0 (da) |
| CH (1) | CH440300A (da) |
| DE (1) | DE1445911A1 (da) |
| DK (1) | DK105983C (da) |
| ES (1) | ES305264A1 (da) |
| FR (2) | FR3878M (da) |
| GB (1) | GB1058738A (da) |
| IL (1) | IL22232A (da) |
| NL (1) | NL6412300A (da) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4056525A (en) * | 1975-06-02 | 1977-11-01 | American Home Products Corporation | 2,3-dialkoxy-3h-1,4-benzodiazepines |
-
1963
- 1963-10-25 US US318783A patent/US3247186A/en not_active Expired - Lifetime
-
1964
- 1964-10-07 CH CH1301964A patent/CH440300A/de unknown
- 1964-10-09 DE DE19641445911 patent/DE1445911A1/de active Pending
- 1964-10-11 IL IL22232A patent/IL22232A/en unknown
- 1964-10-17 FR FR991810A patent/FR3878M/fr not_active Expired
- 1964-10-19 FR FR991849A patent/FR1442304A/fr not_active Expired
- 1964-10-19 DK DK516264AA patent/DK105983C/da active
- 1964-10-20 BR BR163545/64A patent/BR6463545D0/pt unknown
- 1964-10-22 NL NL6412300A patent/NL6412300A/xx unknown
- 1964-10-22 GB GB43159/64A patent/GB1058738A/en not_active Expired
- 1964-10-23 BE BE654734D patent/BE654734A/xx unknown
- 1964-10-24 ES ES0305264A patent/ES305264A1/es not_active Expired
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4056525A (en) * | 1975-06-02 | 1977-11-01 | American Home Products Corporation | 2,3-dialkoxy-3h-1,4-benzodiazepines |
Also Published As
| Publication number | Publication date |
|---|---|
| DE1445911A1 (de) | 1969-04-10 |
| NL6412300A (da) | 1965-04-26 |
| BR6463545D0 (pt) | 1973-07-17 |
| FR3878M (fr) | 1966-01-31 |
| GB1058738A (en) | 1967-02-15 |
| FR1442304A (fr) | 1966-06-17 |
| CH440300A (de) | 1967-07-31 |
| ES305264A1 (es) | 1965-04-16 |
| BE654734A (da) | 1965-04-23 |
| IL22232A (en) | 1968-08-22 |
| DK105983C (da) | 1966-12-05 |
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